DESCRIPTION: The long-term goals are to understand how positional identity of skeletal muscles is established, and specifically, how jaw muscles are specified and maintained. The homeogene Engrailed-2 (En-2) has been shown to be differentially expressed in a subset of jaw muscles (masseter, temporalis). It is first detected in early myogenic founder cells in the first arch, suggesting a role in establishment and development of these muscles. The continued expression of En-2 in adults suggests that it may also play a role in maintenance of mature muscle phenotype. In order to determine the role of En-2 in jaw muscle development, the PI proposes to examine loss-of-function, using En-2 -/- knockouts, and gain of function using En-2 placed under the control of characterized muscle regulatory elements in transient and stable transgenic animals. In order to learn about jaw-specific regulation of En-2, the PI proposes to molecularly dissect the En-2 enhancer with reporter gene constructs in mouse transgenic founders or lines, and to determine the human regulatory elements to aid in identifying conserved sites underlying jaw-specific En-2 expression.